US7862798B2ExpiredUtilityPatentIndex 95

Vitamin-targeted imaging agents

Assignee: ENDOCYTE INCPriority: May 6, 2002Filed: Oct 11, 2006Granted: Jan 4, 2011

Est. expiryMay 6, 2022(expired)· nominal 20-yr term from priority

Inventors:LEAMON CHRISTOPHER P PARKER MATTHEW A

A61K 47/54A61K 47/551A61K 51/00A61K 51/08A61K 51/0459A61K 51/088A61K 49/00A61K 51/0497A61K 51/025A61K 51/0402

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Claims

Abstract

The invention relates to compounds and methods for targeting radionuclide-based imaging agents to cells having receptors for a vitamin, or vitamin receptor binding derivative or analog thereof, by using such a vitamin as the targeting ligand for the imaging agent. The invention provides a compound of the formula for use in such methods. In the compound, V is a vitamin that is a substrate for receptor-mediated transmembrane transport in vivo, or a vitamin receptor binding derivative or analog thereof, L is a divalent linker, R is a side chain of an amino acid of the formula H 2 NCHRCOOH, M is a cation of a radionuclide, n is 1 or 0, K is 1 or 0, and the compound can be in a pharmaceutically acceptable carrier therefor. The vitamin-based compounds can be used to target radionuclides to cells, such as a variety of tumor cell types, for use in diagnostic imaging of the targeted cells.

Claims

exact text as granted — not AI-modified

What is claimed is:

1. A compound of the formula selected from the group consisting of

2. The compound of claim 1 wherein the compound is non-pyrogenic.

3. The compound of claim 1 bound to a radionuclide selected from the group consisting of isotopes of gallium, indium, copper, technetium, and rhenium.

4. The compound of claim 3 wherein the radionuclide is an isotope of technetium.

5. The compound of claim 1 having the formula

6. The compound of claim 1 having the formula

7. The compound of claim 1 having the formula

8. The compound of claim 1 having the formula

9. The compound of claim 1 having the formula

10. The compound of claim 1 having the formula

11. The compound of claim 1 having the formula

12. A composition for diagnostic imaging comprising a compound of the formula selected from the group consisting of

13. The composition of claim 12 wherein the composition is in a dosage form selected from the group consisting of an inhalation dosage form, an oral dosage form, and a parenteral dosage form.

14. The composition of claim 12 wherein the compound is bound to a radionuclide selected from the group consisting of isotopes of gallium, indium, copper, technetium, and rhenium.

15. The composition of claim 14 wherein the radionuclide in the compound is an isotope of technetium.

16. The composition of claim 15 wherein the dosage form is parenteral and is selected from the group consisting of intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, and intrathecal administration.

17. The composition of claim 12 wherein the composition further comprises an unlabeled folate.

18. The composition of claim 13 further comprising a pharmaceutically acceptable carrier and wherein the pharmaceutically acceptable carrier is a liquid carrier.

19. The composition of claim 18 wherein the liquid carrier is selected from the group consisting of saline, glucose, alcohols, glycols, esters, amides, and a combination thereof.

20. A method of imaging a population of cells in an animal wherein said cells are characterized by a vitamin receptor on the surface of said cells, the method comprising the steps of
administering to the animal a composition comprising an effective amount of a compound of the formula selected from the group consisting of

and a pharmaceutically acceptable carrier therefor wherein the compound is bound to a radionuclide; and
monitoring the biodistribution of said compound in the animal.

21. The method of claim 20 wherein the composition is in a dosage form selected from the group consisting of an inhalation dosage form, an oral dosage form, and a parenteral dosage form.

22. The method of claim 20 wherein the radionuclide is selected from the group consisting of isotopes of gallium, indium, copper, technetium, and rhenium.

23. The method of claim 22 wherein the radionuclide in the compound is an isotope of technetium.

24. The method of claim 20 wherein the population of cells in said animal are tumor cells.

25. The method of claim 24 wherein the tumor cells are tumor cells of the ovary.

26. The method of claim 20 wherein the effective amount ranges from about 1 ng to about 1 mg per kilogram of body weight.

27. The method of claim 20 wherein the effective amount ranges from about 100 ng to about 500 μg per kilogram of body weight.

28. The method of claim 20 wherein the effective amount ranges from about 100 ng to about 25 μg per kilogram of body weight.

29. The method of claim 24 wherein the method further comprises the step of monitoring the tumor progression.

30. The method of claim 21 wherein the dosage form is parenteral and is selected from the group consisting of intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, and intrathecal administration.

31. A compound of the formula

32. The compound of claim 31 wherein the compound is non-pyrogenic.

33. A composition for diagnostic imaging comprising a compound of the formula

and a pharmaceutically acceptable carrier therefor.

34. A kit comprising the compound of claim 1 .

35. The kit of claim 24 wherein the kit further comprises a chelating agent and a reducing agent.

36. The kit of claim 35 wherein the kit further comprises a pH-altering agent selected form the group consisting of an acid, a base, and a combination thereof.

37. The kit of claim 35 wherein the chelating agent is sodium α- D -glucoheptonate.

38. The kit of claim 35 wherein the reducing agent is tin (II) chloride dihydrate.

39. The kit of claim 36 wherein the compound has the formula

40. The kit of claim 39 wherein the compound is lyophilized.

41. A method of imaging a population of cells in an animal wherein said cells are characterized by a vitamin receptor on the surface of said cells, the method comprising the steps of
administering to the animal an effective amount of a composition comprising a compound of the formula

and a pharmaceutically acceptable carrier therefor wherein the compound is bound to a radionuclide; and
monitoring the biodistribution of said compound in the animal.

42. The method of claim 41 wherein the composition is in a dosage form selected from the group consisting of an inhalation dosage form, an oral dosage form, and a parenteral dosage form.

43. The method of claim 24 wherein the tumor cells are primary tumor cells.

44. The method of claim 24 wherein the tumor cells are metastasized tumor cells.

45. The compound of claim 4 having the formula

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